This Phase III, Multi-centered clinical trial was designed to determine the effectiveness, tolerability, and safety of different doses of oral type II collagen (Colloral) therapy in patients with RA. 274 patients with RA were entered from 6 sites and randomized to receive placebo or one of four doses (20, 100, 500, and 2500 5g/d) of oral Colloral for 24 weeks. Efficacy parameters were assessed at baseline and monthly during the trial and included swollen and tender joint counts, patient and physician global assessments of disease severity, grip strength, 50 foot walk time, duration of morning stiffness, functional capacity, and serum levels of acute phase reactants. 83% of the patients completed the 24 week trial. Trends were observed for improvement in all of the disease measures for patients in the 20 5g dosage group. In addition, the presence of serum antibodies to type II collagen before treatment was associated with a greater likelihood of response. No significant treatment-related toxicity was noted during the study. Any patient who completed all required dosing and procedures in a previous Colloral study was eligible for enrollment in this open trial. All patients began the open study taking 20 5g each morning in orange juice (or other suitable fruit juice) approximately 20 minutes prior to breakfast. Some patients did not improve at the 20 5g daily dose and their dose was increased incrementally up to 100 5g per day to achieve optimal clinical benefit. Most patients have made follow-up visits every six months for safety and efficacy evaluations. M01RR000300628 Purpose: This was a randomized, double-blind study comparing the safety, patient acceptability and efficacy of RPR 109413 to a licensed IVIG product, Gamimune.-N. Background: Intravenous gammaglobulin (IVIG) preparations have been tested in the US since 1975; ten have been licensed since 1981, seven of which are currently available. The efficacy of IVIG in preventing infections in patients with primary disorders of humoral immunity is well accepted, though it has never been subjected to a controlled double-blind study. A study comparing IVIG to placebo would be considered unethical, though it is possible to compare new products to those that have been licensed for use. In the past several years efforts have focused on developing products with increased safety, especially with regard to the risk of transmitting viral infections such as Hepatitis C. This study proposes to compare the safety, efficacy, and patient acceptability of a new, heat- pasteurized IVIG preparation (RPR 109413) to a licensed preparation, Gamimune.-N. RPR 109413 is a sterile, preservative-free, liquid preparation of unmodified human polyvalent immunoglobulins manufactured by Armour Division of Rhtne-Poulenc Rorer Pharmaceutical. It is prepared from ISG made from a pool of at least 1000 donors. Donors are tested for HIV, HBsAg, Hepatitis C antibody, and increased levels of ALT before being accepted into the pool. The ISG is prepared by the same Cohn fractionation process used for all of the currently licensed products. The Cohn fraction III supernatant is subjected to a viral inactivation step consisting of treatment at 60 C. This treatment was shown to inactivate several surrogate viruses. It is not practical to test inactivation of Hepatitis C directly since the only test system is non- human primates, but these other viruses have been shown to have similar sensitivity to viruses known to be human pathogens. The IgG is adsorbed to reduce the concentration of isoagglutinins, polyethylene glycol is added to precipitate complexes, and the solution is dialyzed to remove the PEG and reduce the sodium concentration. Five percent mannitol is added to enhance stability. The final preparation is at least 98% IgG with trace amounts of IgA and IgM. The amount of IgA is estimated to be < 5 5g/ml, which is comparable to the other low IgA preparation, Gammagard..